Objective
Investigate the impact of socioeconomic status and other demographic variables on adherence to the National Comprehensive Cancer Network ovarian cancer treatment guidelines among patients with stage I/II disease.
Methods
Patients diagnosed with stage I/II epithelial ovarian cancer between 1/1/96–12/31/06 were identified from the California Cancer Registry. Univariate analysis and multivariate logistic regression models were used to evaluate differences in surgical procedures, chemotherapy regimens, and overall adherence to the NCCN guidelines according to increasing SES quintiles (SES-1 to SES-5).
Results
A total of 5445 stage I and II patients were identified. The median age at diagnosis was 54.0 years (range = 18–99 years); 72.5% of patients had stage I disease, while 27.5% had stage II disease. With a median follow-up time of 5 years, the 5-year ovarian cancer-specific survival for all patients was 82.7% (SE = 0.6%). Overall, 23.7% of patients received care that was adherent to the NCCN guidelines. Compared to patients in the highest SES quintile (SES-5), patients in the lowest SES quintile (SES-1) were significantly less likely to receive proper surgery (27.3% vs 47.9%, p < 0.001) or chemotherapy (42.4% vs 53.6%, p < 0.001). There were statistically significant trends between increasing SES and the likelihood of overall treatment plan adherence to the NCCN guidelines: SES-1 = 16.4%, SES-2 = 19.0%, SES-3 = 22.4%, SES-4 = 24.2% and SES-5 = 31.6% (p < 0.001). Multivariate logistic regression analysis revealed that compared to SES-5, decreasing SES was independently predictive of a higher risk of non-standard overall care.
Conclusions
For patients with early-stage ovarian cancer, low SES is a significant and independent predictor of deviation from the NCCN guidelines for surgery, chemotherapy, and overall treatment.
Metformin is a widely used agent for the treatment of diabetes and infertility, however, it has been found to have anti-cancer effects in a variety of malignancies including high grade serous ovarian cancer (HGSC). Studies describing the mechanisms by which metformin affects HGSC are ongoing, but detailed analysis of its effect on the cellular metabolism of both HGSC cells and their precursor, normal fallopian tube secretory epithelial cells (FTSECs), is lacking. We addressed the effects of metformin and the more potent biguanide, phenformin, on HGSC cell lines and normal immortalized FTSECs. Cell proliferation assays identified that FTSECs and a subset of HGSC cell lines are relatively resistant to the anti-proliferative effects of metformin. Bioenergetic and metabolomic analyses were used to metabolically differentiate the metformin-sensitive and metformin-resistant cell lines. Bioenergetically, biguanides elicited a significant decrease in mitochondrial respiration in all HGSC cells and FTSECs. However, biguanides had a greater effect on mitochondrial respiration in metformin sensitive cells. Metabolomic analysis revealed that metformin and phenformin generally induce similar changes in metabolic profiles. Biguanide treatment led to a significant increase in NADH in FTSECs and HGSC cells. Interestingly, biguanide treatment induced changes in the levels of mitochondrial shuttle metabolites, glycerol-3-phopshate (G3P) and aspartate, specifically in HGSC cell lines and not in FTSECs. Greater alterations in G3P or aspartate levels were also found in metformin sensitive cells relative to metformin resistant cells. These data identify bioenergetic and HGSC-specific metabolic effects that correlate with metformin sensitivity and novel metabolic avenues for possible therapeutic intervention.
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